Xywav

Xywav is a prescription oral solution used to treat idiopathic hypersomnia (IH) in adults, and excessive daytime sleepiness (EDS) or cataplexy in patients 7 years and older with narcolepsy. It contains calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate, which all deliver the same active substance, oxybate, also called gamma-hydroxybutyrate (GHB). Xywav is a central nervous system (CNS) depressant.

Xywav is taken at night and is thought to work during sleep to reduce excessive daytime sleepiness and cataplexy (sudden muscle weakness).

Xywav is FDA-approved to treat:

• Idiopathic hypersomnia in adults.
• Cataplexy (sudden loss of muscle strength) or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

Xywav FDA approval was granted on July 22, 2020, to treat cataplexy or excessive daytime sleepiness caused by narcolepsy. FDA approval for Xywav for idiopathic hypersomnia (IH) was granted on August 12, 2021, based on positive results from a clinical trial called Study 2 (NCT03533114).

The exact way Xywav works in narcolepsy and idiopathic hypersomnia is not known. All four ingredients in Xywav deliver the same active substance, oxybate, which is also called gamma-hydroxybutyrate (GHB). GHB is made naturally in the body from GABA, a chemical messenger in the brain. It is thought that Xywav works by acting on GABA-B receptors in the brain during sleep, through its actions on noradrenergic and dopaminergic neurons, as well as thalamocortical neurons.

Xywav works quickly. After a dose, the level of medicine in the blood peaks in about 1.3 hours, and the body clears it quickly, with a half-life of about 40 minutes (0.66 hours). Most of the medicine is broken down to carbon dioxide and breathed out, and less than 5% leaves the body unchanged in the urine.

Yes, Xywav is a Schedule III controlled substance (CIII), which means it has an accepted medical use in treatment in the United States, but it also has a potential for abuse and dependence. Abuse of this medicine may lead to moderate or low physical dependence or high psychological dependence.

The active substance in Xywav, GHB, is a Schedule I controlled substance. Using Xywav for non-medical reasons can lead to the stricter penalties that apply to Schedule I drugs.

Xywav is only available through a Risk Evaluation and Mitigation Strategy (REMS) program called the XYWAV and XYREM REMS, often called the Xywav REMS. This is due to the potential for abuse and risk of the serious side effects of significant CNS and respiratory depression. The REMS program goal is to reduce the risks of serious adverse outcomes resulting from inappropriate prescribing, misuse, abuse, and diversion.

How do I get Xywav?

Xywav is not available from local pharmacies; it is supplied from a Certified Pharmacy under the XYWAV and XYREM REMS:

• your doctor must be specially certified to prescribe Xywav;
• you must be enrolled in the REMS program; and
• Xywav is dispensed only by one specially certified central pharmacy, which ships it directly to you.

Before you receive Xywav, your doctor or pharmacist will make sure you understand how to take it safely, and the risks and benefits of this medicine.

For more information, visit www.XYWAVXYREMREMS.com or call the XYWAV and XYREM REMS at 1-866-997-3688.

Xywav Prescription Form

The Xywav Prescription Form must be filled out at the start of treatment and if there is a break in treatment for 6 months or longer.

Once the Xywav Prescription Form and the patient and prescriber enrollment forms are completed, send them to the XYWAV and XYREM REMS.

The Xywav prescription form is available online to healthcare providers on the Jazz Pharmaceuticals REMS page.

Take Xywav exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. This medicine can cause severe drowsiness and can slow or stop your breathing, even at regular doses or if you are also taking stimulant medicine.

Xywav may be habit-forming. Misuse can cause addiction, overdose, or death. Keep the medication in a place where others cannot get to it. Selling or giving away this medicine is against the law. Do not allow anyone else to use this medicine.

Xywav instructions

Adult Patients with Narcolepsy: twice nightly dosing (once at bedtime and again 2.5 to 4 hours later).Pediatric Patients with Narcolepsy: twice nightly dosing (once at bedtime and again 2.5 to 4 hours later). For children, the first dose can be given at bedtime or after an initial period of sleep.

Adult Dose of Idiopathic Hypersomnia: once or twice nightly dosing

Wait at least 2 hours after eating before taking or giving Xywav.

Xywav is taken as 1 nightly dose, or as 2 doses (once at bedtime and again 2.5 to 4 hours later).

Xywav must be mixed with 2 ounces (1/4 cup) of water in the child-resistant dosing cups provided with the medication.

If you take 2 nightly doses, prepare both doses while you are getting ready for bed. Place the second dose in a secure location next to your bed so you can take it without getting up. You may need to set an alarm to awaken for the second dose.

This medicine works quickly. Most people fall asleep within 5 to 15 minutes.

Take Xywav only while you are sitting in bed, ready for sleep. Some people have fallen asleep while standing or getting up from bed, which has caused injuries serious enough to need treatment in a hospital.

Do not allow a child to use this medicine without adult supervision.

Do not change your dose or stop using this medicine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to stop using this medicine safely. In clinical trials, some people had trouble sleeping (insomnia) after suddenly stopping Xywav, and one person had hallucinations.

Store at room temperature, away from moisture and heat. Keep your medicine in a place where no one can use it improperly. Keep Xywav in its original bottle until you mix it with water. After mixing, keep each dose in the child-resistant pharmacy containers.

How do I throw away Xywav?

When you have finished a bottle of Xywav:

• empty any unused Xywav down the sink drain;
• cross out the label on the bottle with a marker (a marker is not included with your Xywav shipment); and
• put the empty bottle in the trash.

Throw away any mixed dose that has not been taken within 24 hours. Keep Xywav and all medicines out of the reach of children and pets.

Xywav has a boxed warning for central nervous system (CNS) depression and risk for abuse and misuse. A boxed warning is the strongest safety-related warning issued by the FDA.

Central nervous system (CNS) depression.

Xywav can cause severe drowsiness and can slow or stop your breathing, even at regular doses or if you are also taking stimulant medicines. You should not do anything that requires you to be fully awake or is dangerous, including driving a car, using heavy machinery, or flying an airplane for at least 6 hours after taking this medicine. Those activities should not be done until you know how this medicine affects you or your child.

Fatal side effects can occur if you take Xywav with alcohol, other sleep medicines, or other drugs that cause drowsiness or slow your breathing.

Taking Xywav with other medicines that slow down the brain, such as opioid pain medicines, benzodiazepines, sedating antidepressants or antipsychotics, sedating seizure medicines, general anesthetics, or muscle relaxants, can cause breathing problems, low blood pressure, fainting, deep sedation, and death. If you need an opioid pain medicine for a short time, such as before or after surgery, your doctor may pause your Xywav treatment.

Misuse of Xywav can cause breathing problems, seizures, loss of consciousness, or death. Keep the medication in a secure location where others cannot access it.

Abuse and misuse

Xywav may be habit-forming. Misuse can cause addiction, overdose, or death. Keep the medication in a secure location where others cannot access it. Selling or giving away this medicine may harm others and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.

Xywav can cause physical dependence and craving for the medicine when it is not taken as directed.

Other warnings

Depression and suicidality. You should be monitored for emerging or increased depression and suicidality.

This medicine may cause confusion or anxiety.

May cause episodes of sleepwalking.

Do not drink alcohol or take other sleep medicines together with Xywav. Dangerous side effects or death could occur.

Do not give Xywav to anyone with a rare metabolic disorder called succinic semialdehyde dehydrogenase deficiency (which can cause mental or physical impairment).

To make sure you can safely take Xywav, tell your doctor if you have ever had:

• breathing problems;
• lung problems;
• snoring or sleep apnea (breathing stops during sleep);
• depression or suicidal thoughts;
• psychosis or unusual behaviors (anxiety, agitation, paranoia, aggression, hallucinations);
• liver disease; or
• a drug addiction.

This medicine is not approved for patients:

• younger than 7 years old for (EDS) or cataplexy due to narcolepsy.
• younger than 18 years old for idiopathic hypersomnia.

Older adults

Xywav has not been studied in enough people aged 65 and older to know if they respond differently from younger adults. In studies of sodium oxybate in another group of patients, headaches were more common in older adults. Your doctor will usually start you at a lower dose and check you for problems with thinking or movement.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. It is not known if Xywav can harm your unborn baby.

Breastfeeding

Tell your healthcare professional if are breastfeeding or plan to breastfeed. Xywav passes into breast milk. You and your doctor should decide if you or your child will take Xywav or breastfeed.

Common Xywav side effects

Common Xywav side effects may include:

• sleepwalking, talking, or eating in your sleep;
• new sleep problems, strange dreams, night terrors;
• trouble sleeping (insomnia);
• drowsiness, dizziness, tiredness, headache;
• tremors, anxiety;
• dry mouth, nausea, vomiting, diarrhea;
• decreased appetite
• weight loss (especially in children);
• sweating or
• bedwetting (in children).

Serious Xywav side effects

Get emergency medical help if you have signs of an allergic reaction with symptoms of hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

Xywav can cause other serious side effects; call your doctor at once if you have:

• weak or shallow breathing, breathing that stops for short periods of time;
• severe drowsiness, feeling light-headed;
• sleepwalking (may result in an injury), waking and confused behavior at night;
• a seizure;
• depression, anxiety, unusual or unpleasant thoughts;
• feelings of low self-worth, loss of interest in things you once enjoyed;
• confusion, paranoia, hallucinations (seeing or hearing things);
• increased tiredness, trouble concentrating, a change in your weight or appetite, or
• suicidal thoughts or actions.

Other side effects that have been reported since sodium oxybate (the same active ingredient as Xywav) came on the market include joint pain, fluid retention, a hangover feeling, high blood pressure, memory problems, blurred vision, and needing to urinate at night.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or to Jazz Pharmaceuticals at 1-800-520-5568.

Usual Adult Dose of Xywav IH (idiopathic hypersomnia)

Twice-Nightly Dosing Regimen

Initial dose: 4.5 g orally per day, divided and given as 2 equal doses up to 2.25 g each.Maintenance dose: The dose may be increased by 1.5 g orally per night (0.75 g taken at bedtime and 0.75 g) taken 2.5 to 4 hours later) in weekly intervalsMaximum dose: 9 g/day (4.5 g at bedtime and 4.5 g taken 2.5 to 4 hours later)

Once-Nightly Dosing Regimen

Initial dose: 3 g orally per dayMaintenance dose: The dose may be increased by 1.5 g orally per night in weekly intervalsMaximum dose: 6 g/day

Comments Xywav for Idiopathic Hypersomnia:

• This drug may be given in divided doses or as a single dose.
• Dosing may be gradually titrated, and doses should be determined by efficacy and tolerability.
• Patients may respond better with the first dose given at bedtime and the second dose given between 2.5 to 4 hours later.
• During titration, the regimen may be changed between twice nightly and once nightly based on efficacy and tolerability.
• Doses higher than 9 g per night, or single doses higher than 6 g, have not been studied and should not be given.

Use: Xywav for idiopathic hypersomnia

Usual Adult Dose for Narcolepsy

Initial dose: 4.5 g orally per day, divided and given as 2 equal doses of up to 2.25 g/doseMaintenance dose: The dose may be increased by 1.5 g per night (0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later) in weekly intervals up to 6 to 9 g/day.Maximum dose: 9 g/day (4.5g at bedtime and 4.5g taken 2.5 to 4 hours later)Comments:

• Both doses should be diluted at the same time at night.
• The first dose should be taken at bedtime and the other dose should be taken between 2.5 to 4 hours after; some may need to set an alarm to awaken to take the second dose.
• Patients should remain in bed after taking each dose.
• If the second dose is missed, patients should skip the dose and should not take this drug until the next night.
• Dosing may be gradually titrated, and doses should be determined by efficacy and tolerability.

Use: Treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy

Usual Pediatric Xywav Dose for Narcolepsy (7 years and older)

Less than 20 kg:

• Specific dosing recommendations are not available.
• If Xywav is used in patients 7 years of age and older who weigh less than 20 kg, a lower starting dosage, lower maximum weekly dosage increases, and lower total maximum nightly dosage should be considered.

20 to less than 30 kg:

• Initial dose: Up to 2 g orally per night, divided and given as 2 equal doses of up to 1 g/dose
• Dose increases: The dose may be increased by up to 1 g per night (0.5 g taken at bedtime and 0.5 g taken 2.5 to 4 hours later), no more than once a week.
• Maximum dose: 6 g per night (3 g at bedtime and 3 g taken 2.5 to 4 hours later)

30 to less than 45 kg:

• Initial dose: Up to 3 g orally per night, divided and given as 2 equal doses of up to 1.5 g/dose
• Dose increases: The dose may be increased by up to 1 g per night (0.5 g taken at bedtime and 0.5 g taken 2.5 to 4 hours later), no more than once a week.
• Maximum dose: 7.5 g per night (3.75 g at bedtime and 3.75 g taken 2.5 to 4 hours later)

45 kg and greater:

• Initial dose: Up to 4.5 g orally per night, divided and given as 2 equal doses of up to 2.25 g/dose
• Dose increases: The dose may be increased by up to 1.5 g per night (0.75 g taken at bedtime and 0.75 g taken 2.5 to 4 hours later), no more than once a week.
• Maximum dose: 9 g per night (4.5 g at bedtime and 4.5 g taken 2.5 to 4 hours later)

Comments:

• Patients who sleep more than 8 hours/night may be given the first dose at bedtime or after an initial period of sleep.
• Patients weighing less than 20 kg may be given lower initial, maximum, maintenance, and total maximum nightly doses.
• Unequal doses may be required in some patients to attain an optimal response to treatment.
• Both doses should be diluted at the same time at night.
• The first dose should be taken at bedtime, and the other dose should be taken between 2.5 to 4 hours after; some may need to set an alarm to awaken to take the second dose.
• Patients should remain in bed after taking each dose.
• If the second dose is missed, patients should skip the dose and should not take this drug until the next night.
• Dosing may be gradually titrated, and doses should be determined by efficacy and tolerability.

Switching from Xyrem to Xywav

On the first night of Xywav, start at the same dose and dosing schedule as Xyrem (gram for gram). The dose can then be adjusted based on efficacy and tolerability.

Dose adjustments

Liver problems: The recommended starting dose is half the usual starting dose per night, divided into 2 doses.

Divalproex sodium (Depakote): If divalproex is started in someone already taking a stable Xywav dose, a reduction in the Xywav dose of at least 20% is recommended. If Xywav is started in someone already taking divalproex, a lower starting dose of Xywav is recommended. The dose can then be adjusted based on response and tolerability.

Older adults: Dose selection should be cautious, usually starting at the low end of the dosing range.

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

Take Xywav only during your normal sleeping hours (wait at least 2 hours after eating).

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of Xywav can be fatal.

Overdose symptoms may include sweating, vomiting, severe confusion, loss of balance or coordination, or seizure (convulsions). Other overdose symptoms may include agitated or aggressive behavior, headache, blurred vision, muscle jerks, slow or shallow breathing or breathing that stops, slow heartbeat, low body temperature, and coma

Do not drink alcohol. Dangerous side effects or death could occur.

Do not take other sleep medicines together with Xywav.

Xywav will cause drowsiness and can impair your thinking or reactions. You may still feel sleepy the morning after taking this medicine. Wait at least 6 hours or until you are fully awake before you drive, operate machinery, pilot an airplane, or do anything that requires you to be awake and alert

Fatal side effects can occur if you take Xywav with other drugs that cause drowsiness or slow your breathing. Ask your doctor before taking cold or allergy medicine, opioid medication, sedatives, muscle relaxers, seizure medicine, or medicine for depression, anxiety, or mental illness.

If you start or stop taking divalproex (Depakote), your doctor may need to adjust your Xywav dose. Divalproex increases the level of Xywav in your blood, which can affect attention and memory. If you start divalproex while taking Xywav, your Xywav dose will usually be lowered by at least 20%. If you already take divalproex, Xywav will be started at a lower dose.

Other drugs may interact with calcium, magnesium, potassium, and sodium oxybates, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

IH and narcolepsy are chronic sleep disorders that cause severe excessive daytime sleepiness (EDS) and difficulty staying awake.

IH (idiopathic hypersomnia) causes persistent excessive daytime sleepiness even after a full night’s sleep. People with IH may sleep long hours, struggle to wake up, and still feel unrefreshed during the day.

Narcolepsy disrupts the brain’s sleep-wake cycle, leading to overwhelming daytime sleepiness, sudden sleep attacks, and fragmented nighttime sleep. People with narcolepsy may also experience cataplexy, a sudden loss of muscle strength triggered by strong emotions.

The cost of Xywav depends on your dose, your insurance plan and the pharmacy program. See the Xywav price guide for current prices and savings offers.

The manufacturer, Jazz Pharmaceuticals, offers financial support through JazzCares, including a coupon program for people with commercial insurance, help when insurance coverage is delayed or changing, and a patient assistance program for people who qualify based on financial need. You must be enrolled in the XYWAV and XYREM REMS to use these programs. Eligibility rules apply and programs may change, so check the current terms with JazzCares.

Review the Xywav Prescribing Information (PI) for more detailed information about this medicine. The PI contains more detailed information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interactions, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Xywav Prescribing Information is sometimes called Xywav Package or the FDA label.

• Keep out of reach of children.
• Xywav should be stored between 20°C to 25°C (68°F to 77°F).
• Brief storage between 15°C and 30°C (59°F and 86°F) is allowed.
• Dispense in tight containers.
• Solutions prepared following dilution should be consumed within 24 hours.

Xywav Jazz Pharmaceuticals, Inc. Palo Alto, CA 94306.

Active ingredients: calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate (gamma-hydroxybutyrate (GHB)).

Inactive ingredients: purified water and sucralose.

Xywav contains no ingredients made from a gluten-containing grain (wheat, barley, or rye).

Xywav is a clear to slightly opalescent oral solution. Each mL contains 0.234 g calcium oxybate, 0.096 g magnesium oxybate, 0.13 g potassium oxybate, and 0.04 g sodium oxybate (0.413 g total oxybate). It comes in a 180 mL amber bottle with a child-resistant cap and a press-in bottle adaptor, together with an oral dosing syringe and a Medication Guide. The pharmacy provides 2 empty containers with child-resistant caps with each shipment